The Role of Ifosfamide-Doxorubicin Chemotherapy in Histology-Specific, High Grade, Locally Advanced Soft Tissue Sarcoma, Treated With Wide Excision Plus Radiation

Abstract

<h3>Purpose/Objective(s)</h3> To compare long-term outcomes of high grade primary soft tissue sarcoma (STS), using ifosfamide-doxorubicin vs local therapy alone, in histology-specific sarcomas. <h3>Materials/Methods</h3> Retrospective analysis was performed on 127 patients from 2005 to 2018, who had high grade STS of extremity or trunk, > 5cm, that were either Synovial Cell, Dedifferentiated Liposarcoma (DDL), Myxofibrosarcoma, Round Cell Liposarcoma (RCLS), Undifferentiated Pleomorphic Sarcoma (UPS), or Undifferentiated Sarcoma not otherwise specified (NOS), with central pathology review. Ifosfamide-doxorubicin was given over 4-5 cycles, with chemotherapy given in 38 patients, while 89 received local therapy alone. Pre-operative radiation was given in 93 (73.2%), postoperative in 31 (24.4%), and amputation in 3 (2.4%). Multi-variable analysis of prognostic factors was performed, and local-recurrence-free-survival (LRFS), distant-metastases-free-survival (DMFS), disease-specific-survival (DSS), and overall-survival (OS) were estimated using Kaplan-Meier. <h3>Results</h3> Median follow-up was 4.5 years. Younger age (<i>P</i> < 0.0001) and Synovial histology (<i>P</i> = 0.0002) were more likely to undergo chemotherapy. Size > 10cm and trunk location were poor prognostic features on multivariable analysis (MVA) affecting DMFS, DSS, and OS, while DDL had more favorable survival; although size, trunk location, and DDL histology were not significantly different between treatment groups. Sequence of radiation did not significantly affect any of the survival outcomes. Ifosfamide-doxorubicin vs local therapy alone improved 5-year DMFS at 70.2% vs 49.5%, <i>P</i> = 0.02, DSS 83.5% vs 57.9%, <i>P</i> = 0.009, and OS 80.6% vs 53.8%, <i>P</i> = 0.002. Sub-analysis of non-synovial histology still showed a significant improvement in favor of chemotherapy in DMFS, (<i>P</i> = 0.04), DSS (<i>P</i> = 0.02), and OS (<i>P</i> = 0.003). <h3>Conclusion</h3> Ifosfamide-doxorubicin benefits younger patients with > 5cm, high grade, STS of the trunk or extremity in Synovial Cell, DDL, Myxofibrosarcoma, RCLS, UPS, and Undifferentiated Sarcoma NOS.